What's the Deal With the New Plaque Dissolver?
Synthetic HDL shrinks coronary artery plaques
By Richard N. Fogoros, M.D., About.com
Unblock Arteries
In this week=92s Journal of the American Medical Association,
researchers re****t that 5 weekly intravenous injections of a new
substance called ApoA-1 Milano produced significant shrinkage of
plaques in patients with coronary artery disease. This finding, if
confirmed in larger studies, may constitute a revolutionary
breakthrough in the treatment (and possibly the prevention) of
coronary artery disease.
ApoA-1 Milano is essentially a synthetic form of HDL (i.e. good
cholesterol.) High levels of HDL are known to reduce the risk of
coronary artery disease, apparently by =93scouring=94 the blood vessels
and removing cholesterol from vessel walls. This new substance was
discovered by studying 40 people from a small town in Italy, who were
known to live remarkably long and healthy lives despite having
markedly reduced HDL levels. Investigators discovered that these
individuals had a =93mutant=94 form of HDL (the ApoA-1 Milano) that was
not detected by routine blood testing, but that proved to be very
effective in preventing cardiovascular disease. Researchers were able
to synthesize the DNA mutation that produced this new HDL, and
subsequently added this new DNA to a strain of laboratory bacteria =96
thus creating a =93factory=94 for the production of the ApoA-1 Milano.
In the clinical study re****ted this week, 57 patients with coronary
artery plaques were randomized to receive either the ApoA-1 Milano or
placebo. The volume and thickness of their plaques were measured at
the beginning of the study and again after 5 weekly injections. Those
who received the active drug had significantly reduced measures of
volume and thickness of their plaques; those who received placebo did
not.
Since the publication of this study, the print and airwaves media have
been loaded with re****ts from various experts describing how stunned
they are by these results, and hinting as to the far-reaching
implications.
DrRich Comments:
This is indeed a breakthrough study, but we all need to keep a few
things in mind as we consider what this means.
First, there is no evidence that the synthetic HDL used in this study
(and used to good effect by the 40 Italian villagers) is any more
effective than the HDL the rest of us already have. The trick might
not be in the ApoA-1 Milano itself =96 the trick might be in increasing
HDL period, whatever form it takes.
Second, the shrinkage of the plaques observed in this study was
statistically significant, but the plaques certainly didn=92t disappear.
The reduction in plaque volume, for instance, amounted to a few
percent. The stunning breakthrough of this study was not that the
plaques melted away to nothing, but that plaques could be induced to
shrink AT ALL. This constitutes a proof of concept (i.e., that we can
find drugs to shrink plaques) instead of a proof of treatment. More
studies using, for instance, a much longer duration of treatment
(months or years instead of weeks, for instance) will be necessary.
Third, under the best of cir***stances this drug is several years away
from being available outside of the research arena. When it is
available, it is likely to be very expensive (not because drug
companies are evil profit-mongers, but because the manner of producing
this drug is inherently expensive). Long-term intravenous drug therapy
itself is also very expensive, even if the stuff being injected is
cheap.
Fourth, ApoA-1 Milano may not even be the drug that ultimately becomes
the blockbuster plaque-shrinker. Several other drugs targeting HDL are
under active development by a number of companies, and one of them
could easily prove to be more effective or more convenient to
administer than this one.
The bottom line: Plaques can be shrunk, and HDL can do it. Now that
this concept has been =93proven=94 the pharmaceutical houses have a
powerful stimulus to move even more resources toward developing HDL-
targeted therapy. We truly do appear to be on the threshold of a new
era in the management of coronary artery disease. But it=92s very early
in the game.
http://heartdisease.about.com/cs/coronarydisease/a/plaquebuster.htm
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